OVERVIEW: During the initial funding period, the program has made significant advances in molecular imaging through the combined creative efforts of its investigators. These advances in molecular imaging have led to the development of novel molecular imaging reporter molecules which have been used to improve our understanding of cancer etiology, biology, pathophysiology and therapy. In this renewal ICMIC application, we will continue to develop cutting edge approaches for imaging the presence of pre-malignant (dysplastic) tissue and oncogenic signaling molecules in vivo. Project 1 will develop an integrated optical molecular imaging strategy that uses fluorescence peptides as probes to target the presence of premalignant (dysplastic) tissue in vivo. This Project will develop novel optical imaging probes and instruments that can be used in pre-clinical models as well as translated to the clinic as practical screening tools for the early detection of cancer in hollow organs. Project 2 will develop and validate molecular imaging reporters (i.e. EGFR, Met and Akt). Non-invasive imaging in cells and animals will be used to evaluate these novel reporter constructs for detection of key oncogenic signaling pathways. Project 3 will develop molecular imaging tools for imaging of signaling pathways in gliomas and for imaging of the glioma stem cell subpopulation. These tools and concepts should significantly aid in our preclinical drug development process and provide insights into more efficacious combination therapy strategies for brain tumors. The proposal includes a Career Development Program which provides the opportunity to train and interact with young, enthusiastic molecular imaging investigators. The Pilot Program will enable recruitment of outstanding scientists to the molecular imaging field by providing funding, ideas and resources to facilitate ongoing research. Core A, the administrative core will provide administrative and statistical support to all projects and will also facilitate External and Internal scientific review of all projects. The imaging Core (Core B) will provide imaging expertise and equipment for all of the animal imaging needs of this ICMIC. The Biostatistics Core (Core C) will provide for all of the biostatistical analysis of all of the Projects, Pilot Projects and Career Development Awardees. One of the central goals of the UM-ICMIC program is to bridge the great divide between quality patient care and laboratory studies in cancer research. This continues to be the driving force in the current proposal.